AimsAn ongoing outbreak of 2019 novel coronavirus (SARS-CoV-2) diseases (COVID-19) has been spreading in multiple countries. One of the reasons for the rapid spread is that the virus can be transmitted from infected individuals without symptoms. Revealing the pathological features of early phase COVID-19 pneumonia is important to the understanding of its pathogenesis. The aim of this study was to explore pulmonary pathology of early phase COVID-19 pneumonia in a patient with a benign lung lesion. Methods and resultsWe analyzed the pathological changes of lung tissue from a 55-year-old female patient with early phase SARS-CoV-2 infection. In this case, right lower lobectomy was performed for a benign pulmonary nodule. Detailed clinical, laboratory and radiological data were also described. This case was confirmed to have preoperative SARS-CoV-2 infection by real-time RT-PCR and RNA in situ hybridization on surgically removed lung tissues. Histologically, COVID-19 pneumonia was characterized by exudative inflammation. The closer to the visceral pleura, the more severe the exudation of monocytes and lymphocytes. Perivascular inflammatory infiltration, intraalveolar multinucleated giant cells, pneumocyte hyperplasia and intracytoplasmic viral-like inclusion bodies were seen. However, fibrinous exudate and hyaline membrane formation, which were typical pulmonary features of SARS pneumonia, were not evident in this case. Immunohistochemical staining results showed that an abnormal accumulation of CD4+ helper T lymphocytes and CD163+ M2 macrophages in the lung tissue. Accepted ArticleThis article is protected by copyright. All rights reserved ConclusionThe results highlighted the pulmonary pathological changes of early phase SARS-CoV-2 infection and suggested a role of immune dysfunction in the pathogenesis of COVID-19 pneumonia.

Metastasis is the major cause of death in patients with non-small cell lung cancer (NSCLC), and epithelial-mesenchymal transition (EMT) has been observed to be one of the key regulators of metastasis in certain cancers as it confers an invasive phenotype. CD133 is a widely used cancer stem cell (CSC) marker, and CD133-positive cancer cells are thought to be tumor-initiating cells with CSC characteristics, while CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in NSCLC tissues and participates in cancer progression by regulating cell anti-apoptosis. We previously demonstrated that CXCR4 promotes NSCLC chemoresistance by upregulating CYP1B1, however, the relationship of CD133, CXCR4 and EMT processes in NSCLC metastasis are unclear. In this study, we detected a CD133 and CXCR4 high expression in tissue specimens from 64 NSCLC patients by immunohistochemistry, of which CD133 and CXCR4 were found to be positively associated with metastatic NSCLC patients. CD133 was found to promote NSCLC tumorigenesis and mediated the expression of CXCR4. Furthermore, CD133/CXCR4 co-expression was found to be an independent prognostic factor as shown by univariate and multivariate Cox regression analysis, and was observed to regulate the expression of EMT-related molecules and transcriptional factors in NSCLC. In addition, our results showed that E-cadherin and Vimentin were simultaneously downregulated and upregulated, in CD133+CXCR4+ A549 cells, respectively. While E-cadherin was upregulated and Vimentin was downregulated in metastatic NSCLC patients. Vimentin expression was also observed to have a positive correlation with CD133/CXCR4 co-expression in NSCLC patients and survival analysis results suggested that Vimentin high expression might be significantly associated with poor survival rates of the patients. Thus, these results suggest that the CD133/CXCR4/EMT axis may be a prognostic marker and may provide novel targets for combinational therapies in the treatment of NSCLC.

Aberrant microRNAs are widely identified in multiple cancers, including lung cancer. miR‐135a‐5p can function as a significant tumor regulator in diverse cancers via impacting multiple genes in oncogenic pathways. Nevertheless, the biological role of miR‐135a‐5p in lung cancer is poorly known. Here, we investigated its function in lung cancer. As exhibited, miR‐135a‐5p was elevated in lung cancer cells in contrast to BEAS‐2B cells. Then, we inhibited miR‐135a‐5p expression by transfecting LV‐anti‐miR‐135a‐5p into lung cancer cells. As displayed, miR‐135a‐5p was obviously reduced in A549 and H1299 cells. Knockdown of miR‐135a‐5p repressed lung cancer cell growth and cell proliferation. Meanwhile, cell colony formation capacity was depressed, cell apoptosis was enhanced and cell cycle progression was blocked in G1 phase by inhibition of miR‐135a‐5p in vitro. Additionally, the migration and invasion of A549 and H1299 cells was strongly depressed by LV‐anti‐miR‐135a‐5p. For another, by using informatics analysis, lysyl oxidase‐like 4 (LOXL4) was speculated as the downstream target of miR‐135a‐5p. We validated their direct correlation and moreover, overexpression of miR‐135a‐5p restrained LOXL4 levels in lung cancer cells. Subsequently, we proved that miR‐135a‐5p promoted lung cancer development via targeting LOXL4 by carrying out the in vivo assays. Taken these together, our study revealed miR‐135a‐5p might be indicated as a perspective for lung cancer via targeting LOXL4.

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Chemoresistance is the main cause of treatment failure and high mortality in advanced lung cancer. Cisplatin, an important chemotherapeutic agent for lung cancer, has been observed to show enormously reduced chemotherapeutic efficacy owing to the development of chemoresistance. CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in non-small cell lung cancer (NSCLC) tissues and participates in cancer progression by regulating cell growth, apoptosis or invasion. In this study, we therefore investigated whether CXCR4 plays a role in the cisplatin associated resistance in NSCLC. We detected the expression of CXCR4 in tissue specimens from 64 NSCLC patients by immunohistochemistry. Cisplatin-resistant NSCLC cells A549/DDP and its parental A549 cells were employed in this study. RNA interference was performed to silence the CXCR4. The influence of CXCR4 on tumor cell chemoresistance, apoptosis and growth, as well as the relationship between CXCR4 and the expression of cytochrome p450 associated molecule CYP1B1 in NSCLC were evaluated. Finally, we found CXCR4 was significantly highly expressed in cisplatin-resistant NSCLC patients and the A549/DDP cell line. CXCR4 inhibition by siRNA reversed chemoresistance and decreased tumor cell proliferation. Bioinformatics analysis showed that the expression of CYP1B1 had a positive correlation with CXCR4, the CYP1B1 silencing significantly decreased CXCR4 expression levels and cisplatin resistance. Immunohistochemistry also verified that CYP1B1 was upregulated in NSCLC tissues of cisplatin-resistant patients. In conclusion, our results indicate that overexpression of CXCR4 in NSCLC promotes cisplatin resistance via CXCR4-mediated CYP1B1 upregulation. Thus, it can be used as a potential therapeutic target in NSCLC chemoresistance patients and be used as a clinical predictor of cisplatin response.